Type 1 diabetes—typically diagnosed in children—results from the autoimmune destruction of insulin-secreting β cells in the pancreas, with the consequent failure of glucose regulation. The direct medical costs approach $7 billion annually, with each patient spending over $100,000 in their lifetime. Although the disease can often be managed with daily insulin injections, this treatment does not even approach a cure. Although transplantation of β cells from cadavers to patients has shown promise, the scarcity and variability of these cells limits their utility. Pagliuca et al. now provide a rapid and efficient protocol for the large-scale production of mature, functional β cells from human pluripotent stem cells or potential transplantation to type 1 diabetes patients.

Although pluripotent stem cells can in principle generate all cell types of the adult body, in practice it is difficult to grow sufficient numbers of mature functional cells from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). To date, the resulting cells are relatively immature and cannot secrete sufficient insulin in response to repeated glucose challenges. In the current study, the authors report an optimized and efficient protocol for the generation of human pancreatic β cells from hESC and hiPSC lines in less than 5 weeks in vitro. The method was reproducible across 12 independent human pluripotent stem cell lines and scalable to produce the nearly 1 billion β cells required for human therapy. Like bona fide human β cells, the derived β cells could repeatedly sense glucose levels and respond by secreting proper amounts of insulin. In addition, they functioned in vivo in a genetic mouse model of diabetes: the transplanted mice showed restored fasting blood glucose levels, the sustained ability to respond to glucose challenges with human insulin, and extended survival.

Pluripotent stem cells are a promising source of cells to replace damaged or diseased tissue by transplantation, but we need to be able to produce large quantities of well-differentiated cells. These new data bring us one step closer to that goal for pancreatic β cells, but we still face a substantial challenge in preventing the transplanted β cells from rejection by the recipient patient.